COVID-19 shots have now been FDA-authorized for emergency use for babies, toddlers and preschoolers, as well as recommended by the CDC, but they remain controversial.

Pre-orders from state health departments for the shots were due by Tuesday, June 14, before the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) had even heard presentations from drug sponsors Pfizer and Moderna. Forty-nine states – every state except Florida – made pre-orders. (Physicians in Florida can order these shots directly from the federal government, which is making all purchases from Pfizer and Moderna.)

VRBPAC voted unanimously in favor of authorization for both products – two shots of Moderna’s 25 micrograms each for ages 6 months through 5 years, and three shots of Pfizer’s three micrograms for ages 6 months through 4 years – as well as for authorizing Moderna’s adult shots for kids as young as 6. FDA issued the updated Emergency Use Authorizations (EUAs) just 45 minutes before the CDC’s Advisory Committee on Immunization Practices (ACIP) met to discuss recommending COVID-19 shots for children ages 6 months through 4 years.

ACIP voted unanimously to recommend the shots from both manufacturers for all children 6 months old and up.

Heart damage

in young men

Although FDA’s own internal analysis of vaccine adverse events did not identify a “significantly higher” risk of myocarditis/pericarditis [inflammation of the heart muscle or the sac surrounding the heart] following the second Moderna injection as compared with the second Pfizer injection among males 18–25 years of age, other nations have identified the Moderna shots as significantly riskier for this demographic group than the Pfizer injections. Several European countries, including France and Germany, have banned the administration of Moderna’s COVID-19 shots in men younger than 30.

FDA’s own analysis was not statistically high-powered enough to make a determination, although raw U.S. data from passive surveillance show Moderna’s myocarditis/pericarditis risk in men ages 18 through 25 as 1.1 times higher than Pfizer’s, and active surveillance shows a 130 percent to 150 percent elevation in risk from the Moderna product.

Any excess risk from the Moderna product is on top of a high observed rate of heart damage for young males who have taken the Pfizer product. The overall rate of myocarditis or pericarditis in recipients of the Pfizer mRNA shots is substantially higher than the “background” rate – the expected rate in a world without mRNA injections. For example, boys ages 12 through 15 who received two doses of the Pfizer product suffered myocarditis/pericarditis at a rate 40 to 80 times what physicians usually observe in boys of that age range. Young men between 18 and 25 who took one dose of the Pfizer product had heart injuries between twofold and eightfold higher than they would have in a world with no COVID-19 shots.

Unclear mechanism of action

When asked, Pfizer’s representative couldn’t explain to VRBPAC members how the products work. Dr. Jay Portnoy, a professor of pediatrics who serves as the consumer representative on the committee, pointed out that the Pfizer injections for babies are three micrograms, compared with the Moderna shots, which are 25 micrograms. He asked Dr. Bill Gruber of Pfizer, “The purpose of mRNA is to induce protein production. Is your mRNA just more efficient at making cells produce spike protein?”

Gruber responded, “Obviously we don’t have a complete understanding of the way the vaccine works in producing an immune response, so you have to go by the results. After a third dose, just as in adults with higher doses, we’re getting an immune response [measured in terms of antibody levels] that’s comparable.”

Public commenters raised the question of biodistribution of the lipid nanoparticles that encapsulate the mRNA in both manufacturers’ products: where they go, and how long the cells where they end up continue to produce the Wuhan spike protein. (Neither FDA nor vaccine sponsors typically answer public comments; the comments are for the consideration of the committee.)

Sparse efficacy data for babies and preschoolers

Perhaps more concerning, data for children ages 6 months through 23 months, and children ages 2 through 4 years (for Pfizer) and 5 years (for Moderna) did not demonstrate efficacy (preventing symptomatic illness) with high statistical confidence. Added to this weak data is some question as to whether an “emergency” even exists for preschool children and babies, who have a nearly 100 percent survival rate from COVID-19, and more than half of whom (according to CDC data) have already experienced the disease.

Although Pfizer’s Bill Gruber presented slides showing high VE, the 95 percent confidence intervals were extremely wide. During the committee discussion, Dr. Paul Offit of Children’s Hospital of Philadelphia noted that “Protective efficacy was listed, but those are based on very small numbers, 7 cases in one instance, 3 cases in another. It’s hard to feel comfortable because the numbers are so low.”

Moderna presented data showing VE between 12.5 percent and 54.0 percent for children ages 2–5 using the CDC case definition of COVID-19, and between 19.8 percent and 63.8 percent using the company’s own definition of COVID-19 disease. Moderna’s baby and toddler VE (95 percent confidence interval) ranged from 21.4 percent and 68.6 percent using the CDC definition, and -27.7 percent and 62.0 percent using the company’s own definition. The wide confidence intervals are indicative of the small number of cases used to calculate VE.

Both companies made additional efficacy claims based on “immunobridging,” which is comparing the antibody levels of injected babies, toddlers and preschoolers with antibody levels of older vaccinated study participants, and assuming actual efficacy based on those numbers.

Dramatic public comment

The comments during the portion of the second day of the meeting open to the public were largely in favor of EUA expansion for both companies. This majority was driven by several parents of children younger than five years of age, who told the committee that they have essentially kept their children from all social contact for the past two years.

Caroline Bishop, an associate professor of classics at Texas Tech University, said that when her husband’s workplace dropped its mask mandate, he “made the heartbreaking decision to move out to our guest house.” Prof. Bishop described her 14-month-old daughter calling, “Dada” when she sees her father out in the yard and crying because she isn’t allowed to touch him. She said that she received proof that her fears were justified when her husband, who is double-vaccinated and boosted, contracted COVID-19 last week. She begged the committee to vote to allow babies to receive the shots.

An alternate viewpoint was expressed by Rep. Louis Gohmert of Texas, who is one of 18 signatories to a June 8, letter from congressmen to the FDA. During the public comment, Gohmert posed a subset of the questions that he and his colleagues posed in their letter, including “What is the cardiac risk factor in administering these COVID vaccines to children?” and “Is it possible that the proposed COVID vaccines in young children could create increased risk from future novel COVID variants?”

Gohmert further questioned the fairness of the liability shield that protects COVID-19 shot providers and compels individuals alleging injury to seek compensation from the federal government, which usually denies it. He added that he was “working on […] a bill […] to allow civil and criminal liabilities to vaccine providers, and accessories, despite an EUA, which should force more sensitivity to vaccine harm to our children.”

In explaining their “yes” votes, most VRBPAC members said they wanted to give parents a choice, especially those who had chosen extreme social isolation for their children. However, most offered only tempered support for the two products.

Dr. Michael Nelson, chief of the Asthma, Allergy, and Immunology Division at the UVA School of Medicine, expressed concern that the children in the trials received their COVID-19 shots with a two-week buffer from flu shots and a one-month buffer from any other shot. No children were studied who received COVID-19 shots at the same time as other routine pediatric immunizations.

Along with Dr. Archana Chatterjee and Dr. Mark Sawyer, Dr. Nelson noted that children in the real world receive many shots in one day. He warned Moderna and Pfizer, “Coadministration is something I’ve been thinking about. I will tell you that if we don’t get a quick answer, that is going to be a barrier to BLA [biological license application, or full approval of a vaccine]. Having to get it in isolation is going to be a barrier for families.”

Other members sought to put parents’ fears in perspective. Dr. Cody Meissner of Tufts Medical School pointed out that in the past two years, 442 children younger than 5 have died while infected with SARS-CoV-2, approximately 220 deaths per year. He contextualized that statistic with the fact that 270 Americans are struck by lightning in any given year.

“We’d be talking about vaccinating close to 20 million in order to prevent 200 deaths,” Dr. Meissner said. “I think the vaccine should be available for high-risk children and for families who are so concerned that they’re troubled by that risk ratio, but parents should understand how small these numbers are.”